An animal study published in the journal found that gene editing could be a potential treatment for anxiety and alcohol use disorders in adolescents who drink alcohol. Science Advances.
The study, published by researchers at the University of Illinois at Chicago, is examining the health effects of drinking at an early age.
In a preliminary study, the UIC team found that drinking alcohol in adolescence immediately altered the cytoskeleton-linked protein in the amygdala of both the rodent and human amygdala, reducing Arc expression in the amygdala of both rodents and humans. . This epigenetic reprogramming of the Arc gene in the brain’s emotional and memory center tends to lead to anxiety and alcohol use disorders in adulthood.
In a new study, researchers showed that this lifelong epigenetic reprogramming could be reversed by genetic modification.
“Early alcohol consumption can have a long-lasting and significant effect on the brain, and the results of this study prove that gene repair is a potential antidote to these effects, suggesting factory resetting the brain if desired,” said Subhash Pandey, the study’s senior author. Professor of Psychiatry at Flaherty and Director of the Alcohol Research Center for Epigenetics at UIC.
Pandey and his team used a gene-correcting tool called CRISPR-dCas9 in their experiments to control histone acetylation and methylation in the Arc gene in large rat models. These processes make genes more or less available for activation.
First, researchers studied large rats that regularly consumed alcohol during adolescence, which ranged from 10 to 18 years of age. They observed normalized Arc gene expression when dCas9 was used to acetylate a process that softens chromatin and allows transcription factors to bind to DNA. In addition, anxiety and alcohol consumption decreased.
Anxiety is measured by behavioral testing, for example, by documenting the reconnaissance activity of rats in labyrinth tests, and by monitoring the amount of fluid consumed when rats are offered a choice of two bottles. tap water, sugar water and alcohol of various concentrations (3%, 7% and 9%).
In the second model, the researchers studied adult rats without early exposure to alcohol. When the inhibitory dCas9 was used to promote methylation, which inhibited the binding of chromatin-hardening and transcription factors to DNA, decreased Arc expression, increased anxiety rates, and increased alcohol consumption.
“These findings suggest that epigenomic editing in the amygdala may improve the psychopathology of adults after alcohol exposure in adolescents,” the authors say.
“Adolescent drinking is a serious public health problem, and this study not only helps us better understand what happens when the brain develops when exposed to high concentrations of alcohol, but most importantly, it gives us hope that one day we will have effective treatment.” For multidisciplinary diseases, ”Pandey said, as well as Jesse Brown’s senior research career at VA Medical Center. “The two-sided view of this effect confirms the importance of the Arc-enhancing gene in the amygdala in the epigenetic reprogramming of adolescent alcohol consumption.”
The authors of the study, John Peyton Bonsac, Huaibo Zhang, Gabriela Wandling, Dongong Hee, Evan Kizar, and Amy Lasek, all from UIC, said that “targeted epigenomic editing improves adult anxiety and adolescent alcoholism after alcohol exposure.”
Alcohol consumption during adolescence increases the risk of anxiety in later life
John Peyton W. Bohnsack et al, Targeted epigenomic editing improves adult anxiety and excessive drinking after adolescent alcohol exposure, Science Advances (2022). DOI: 10.1126 / sciadv.abn2748
Presented by the University of Illinois at Chicago
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